Evidence map›Paper›PMID 26723758›Full record

ArticleThe Lancet. Infectious diseases2016

Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study.

Elizabeth H Byrne, Melis N Anahtar, Kathleen E Cohen, Amber Moodley, Nikita Padavattan, Nasreen Ismail, Brittany A Bowman, Gregory S Olson, Amanda Mabhula, Alasdair Leslie and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 5 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 5 syntheses or guidelines pooled it, 107 citations in OpenAlex.

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  14. Genital inflammatory status and the innate immune response to contraceptive initiation.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022
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  20. The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 3 countries.

Elizabeth H ByrneRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Melis N AnahtarRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Kathleen E CohenRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Amber MoodleyFemales Rising through Education, Support, and Health, Durban, KwaZulu-Natal, South Africa.
Nikita PadavattanHIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Nasreen IsmailHIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Brittany A BowmanRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Gregory S OlsonRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Amanda MabhulaKwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Alasdair LeslieKwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Thumbi Ndung'uRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA; HIV Pathogenesis Programme, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Chariteplatz, Berlin, Germany.
Bruce D WalkerRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Musie S GhebremichaelRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Krista L DongFemales Rising through Education, Support, and Health, Durban, KwaZulu-Natal, South Africa.
Douglas S KwonRagon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA, USA. Electronic address: dkwon@mgh.harvard.edu.
Ragon Institute of MGH, MIT and Harvard · USUniversity of KwaZulu-Natal · ZAMassachusetts General Hospital · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Inflammation and the vaginal metagenome in HIV acquisitionR01AI111918 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI KWON, DOUGLAS, VIRGIN, HERBERT W · 2014 to 2017
$2.5M
Howard Hughes Medical InstituteNIAID NIH HHS 1R01AI111918NIAID NIH HHS R01 AI111918NIGMS NIH HHS T32 GM007266NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753Wellcome Trust 097410
6 · The paper itself

Abstract

backgroundThe use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract.

methodsIn this prospective cohort, we enrolled HIV-negative South African women aged 18-23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods.

findingsBetween Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12·06 per 100 person-years, 95% CI 6·41-20·63) than women using no long-term contraception (3·71 per 100 person-years, 1·36-8·07; adjusted hazard ratio [aHR] 2·93, 95% CI 1·09-7·868, p=0·0326). HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0·0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0·0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives.

interpretationInjectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure.

fundingThe Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases.

Indexed as

AdolescentCohort StudiesContraceptionContraceptive Agents, FemaleFemaleHIV-1HIV InfectionsHumansIncidenceInjectionsProgestinsProportional Hazards ModelsProspective StudiesRiskSouth AfricaYoung AdultContraceptive Agents, FemaleProgestins

Identifiers

PMID26723758
PMCPMC5294917
OpenAlexW2216450681

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.